Cellular DNA is continuously exposed to insults from exposure to endogenous and exogenous alkylating agents and oxidative stress. Base excision repair appears to be primarily responsible for the elimination of most of these deleterious DNA lesions (Wood (1996) Annu. Rev. Biochem. 65:135-167). In addition to DNA lesions induced by these agents, spontaneous depurination/depyrimidination could introduce a significant amount of apurinic/apyrimidinic (AP) sites under physiological conditions (Nakamura, et al. (1998) Cancer Res. 58:222-225). Using a combination of an aldehyde reactive probe and slot blot technique, the spontaneous depurination rate under physiological conditions was found to be 1.5 AP sites per 106 nucleotides per day, which corresponds to 9000 AP sites per cell per day (Nakamura, et al. (1998) Cancer Res. 58:222-225). Modified bases and AP sites introduce DNA single strand breaks as intermediates of base excision repair pathway (Krokan, et al. (1997) Biochem. J. 325:1-16). In this process, a DNA glycosylase cleaves the N-glycosylic bond between modified or even normal bases and deoxyriboses, leaving AP sites (Krokan, et al. (1997) Biochem. J. 325:1-16; Lindahl (2000) Mutat. Res. 462:129-135). The AP sites generated by the DNA glycosylase are subsequently incised by a class II AP endonuclease (Demple and Harrison (1994) Annu. Rev. Biochem. 63:915-948), resulting in a 3′-hydroxyl group and a 5′-deoxyribosephosphate (5′-dRp). After excision of 5′-dRp by DNA polymerase β (β-pol), repair is completed by the polymerase and ligase activities of β-pol and DNA Ligase, respectively. Furthermore, reactive oxygen species (ROS) also induce lesions by hydrogen abstraction of the deoxyribose, frequently producing oxidized AP sites as well as DNA single strand breaks (Breen and Murphy (1995) Free Radic. Biol. Med. 18:1033-1077). In B-form duplex DNA, hydrogen atoms at the C-4′ and C-5′ positions of deoxyribose are the most accessible to ROS (Von Sonntag (1987) In: The Chemical Basis of Radiation Biology, pp. 238-249, Taylor and Francis, London), leading to 3′- and 5′-terminal lesions, respectively. Therefore, DNA single strand breaks are one of the most frequent DNA lesions in mammalian cells even under physiological conditions. Single cell agarose gel electrophoresis, i.e., the Comet assay, is a well-known and sensitive assay to assess the amount of single strand breaks and their repair (Tice, et al. (2000) Environ. Mol. Mutagen. 35:206-221). However, this assay usually requires alkaline conditions to denature DNA for subsequent gel electrophoresis. Alkylating agents and oxidants introduce either alkaline-labile base lesions or AP sites leading to single strand breaks under basic conditions (Burrows and Muller (1998) Chem. Rev. 98:1109-1152; Miyamae, et al. (1997) Mutat. Res. 393:107-113). Artifactual formation of single strand breaks may therefore be introduced during DNA extraction. Therefore, it is difficult to accurately determine the number of single strand breaks and an imbalance in their repair using isolated cellular DNA.